简介：Neurodegenerativedisordersaffectmorethan30millionindividualsthroughouttheworldandleadtosignificantdisabilityaswellasdeath.Thesestatisticswillincreasealmostexponentiallyasthelifespanandageofindividualsincreasegloballyandindividualsbecomemoresusceptibletoacutedisorderssuchasstrokeaswellaschronicdiseasesthatinvolvecognitiveloss,Alzheimer’sdisease,andParkinson’sdisease.Currenttherapiesforsuchdisordersareeffectiveonlyforasmallsubsetofindividualsorprovidesymptomaticreliefbutdonotalterdiseaseprogression.Oneexcitingtherapeuticapproachthatmayturnthetideforaddressingneurodegenerativedisordersinvolvesthemammaliantargetofrapamycin(mTOR).mTORisacomponentoftheproteincomplexesmTORComplex1(mTORC1)andmTORComplex2(mTORC2)thatareubiquitousthroughoutthebodyandcontrolmultiplefunctionssuchasgenetranscription,metabolism,cellsurvival,andcellsenescence.mTORthroughitsrelationshipwithphosphoinositide3-kinase(PI3-K)andproteinkinaseB(Akt)andmultipledownstreamsignalingpathwayssuchasp70ribosomalS6kinase(p70S6K)andprolinerichAktsubstrate40kDa(PRAS40)promotesneuronalcellregenerationthroughstemcellrenewalandoverseescriticalpathwayssuchasapoptosis,autophagy,andnecroptosistofosterprotectionagainstneurodegenerativedisorders.TargetingbymTORofspecificpathwaysthatdrivelong-termpotentiation,synapticplasticity,andβ-amyloidtoxicitymayoffernewstrategiesfordisorderssuchasstrokeandAlzheimer’sdisease.Overall,mTORisanessentialneuroprotectivepathwaybutmustbecarefullytargetedtomaximizeclinicalefficacyandeliminateanyclinicaltoxicsideeffects.

简介：Therearecurrentlynofederallyapprovedneuroprotectiveagentstotreattraumaticbraininjury.Progesterone,ahydrophobicsteroidhormone,hasbeenshowninrecentstudiestoexhibitneuroprotectiveeffectsincontrolledcorticalimpactratmodels.Aktisaproteinkinaseknowntoplayaroleincellsignalingpathwaysthatreduceedema,inflammation,apoptosis,andpromotecellgrowthinthebrain.ThisstudyaimstodetermineifprogesteronemodulatesthephosphorylationofAktviaitsthreonine308phosphorylationsite.Phosphorylationatthethreonine308siteisoneofseveralsitesresponsibleforactivatingAktandenablingtheproteinkinasetocarryoutitsneuroprotectiveeffects.ToassesstheeffectsofprogesteroneonAktphosphorylation,C57BL/6miceweretreatedwithprogesterone(8mg/kg)at1(intraperitonally),6,24,and48hours(subcutaneously)postclosed-skulltraumaticbraininjury.Thehippocampuswasharvestedat72hourspostinjuryandpreparedforwesternblotanalysis.TraumaticbraininjurycausedasignificantdecreaseinAktphosphorylationcomparedtoshamoperation.However,micetreatedwithprogesteronefollowingtraumaticbraininjuryhadanincreaseinphosphorylationofAktcomparedtotraumaticbraininjuryvehicle.Ourfindingssuggestthatprogesteroneisaviabletreatmentoptionforactivatingneuroprotectivepathwaysaftertraumaticbraininjury.

简介：Vagusnervestimulationexertsprotectiveeffectsagainstischemicbraininjury;however,theunderlyingmechanismsremainunclear.Inthisstudy,aratmodeloffocalcerebralischemiawasestablishedusingtheocclusionmethod,andtherightvagusnervewasgivenelectricalstimulation(constantcurrentof0.5mA;pulsewidth,0.5ms;frequency,20Hz;duration,30seconds;every5minutesforatotalof60minutes)30minutes,12hours,and1,2,3,7and14daysaftersurgery.Electricalstimulationofthevagusnervesubstantiallyreducedinfarctvolume,improvedneurologicalfunction,anddecreasedtheexpressionlevelsoftumornecrosisfactor-αandinterleukin-6inratswithfocalcerebralischemia.Theexperimentalfindingsindicatethattheneuroprotectiveeffectofvagusnervestimulationfollowingcerebralischemiamaybeassociatedwiththeinhibitionoftumornecrosisfactor-αandinterleukin-6expression.

简介：Therearefewstudiesontheneuroprotectiveeffectsofsyringaldehydeinaratmodelofcerebralischemia.Thestudyaimedtoelucidatethemechanismsunderlyingtheneuroprotectiveeffectsofsyringaldehydeonischemicbraincells.Ratmodelsofcerebralischemiawereintraperitoneallyadministeredsyringaldehyde.At6and24hoursaftersyringaldehydeadministration,celldamageinthebrainofcerebralischemiaratswasobviouslyreduced,superoxidedismutaseactivityandnuclearrespiratoryfactor1expressioninthebraintissueweremarkedlyincreased,malondiadehydelevelwasobviouslydecreased,apoptosis-relatedcysteinepeptidasecaspase-3and-9immunoreactivitywasobviouslydecreased,andneurologicalfunctionwasmarkedlyimproved.Thesefindingssuggestthatsyringaldehydeexertsneuroprotectiveeffectsoncerebralischemiainjurythroughanti-oxidationandanti-apoptosis.

简介：Multiplesclerosis(MS)isachronicautoimmunediseaseofthecentralnervoussystem(CNS)characterizedbycoexistingprocessesofinflammation,demyelination,axonalneurodegeneration,andgliosis.Itisthemostcommondisablingneurologicaldiseaseinyoungadulthood.Althoughautoimmuneinflammationcontributestoaxonalpathology

简介：1-methyl-4-phenylpyridiniumion(MPP+)inducesendoplasmicreticulumstressandactivatescaspase-12inPC12cells,leadingtoneuronalapoptosis.However,theunderlyingmolecularmechanismremainsunknown.Thepresentstudyinvestigatedtheregulatoryeffectsofnervegrowthfactor(Aktactivator)andlithiumchloride(glycogensynthasekinase-3βinhibitor)ontheendoplasmicreticulumstresssignalingpathway.TheresultsrevealedthatMPP+inducedexpressionofBipandC/EBPhomologousprotein.TheupregulationofBipandC/EBPhomologousprotein,aswellasthedecreasedpro-caspase-12levelinducedbyMPP+wereinhibitedbypretreatmentofthenervegrowthfactororlithiumchloride.Theseresultssuggestthatthephosphatidylinositol3kinase-Akt-glycogensynthasekinase-3βpathwayisinvolvedinMPP+-inducedendoplasmicreticulumstress.

简介：Ischemicpreconditioningelicitedbyanon-fatalbriefocclusionofbloodflowhasbeenappliedforanexperimentaltherapeuticstrategyagainstasubsequentfatalischemicinsult.Inthisstudy,weinvestigatedtheneuroprotectiveeffectsofischemicpreconditioning(2-minutetransientcerebralischemia)oncalbindinD28kimmunoreactivityinthegerbilhippocampalCA1areafollowingasubsequentfataltransientischemicinsult(5-minutetransientcerebralischemia).AlargenumberofpyramidalneuronsinthehippocampalCA1areadied4daysafter5-minutetransientcerebralischemia.IschemicpreconditioningreducedthedeathofpyramidalneuronsinthehippocampalCA1area.CalbindinD28kimmunoreactivitywasgreatlyattenuatedat2daysafter5-minutetransientcerebralischemiaanditwashardlydetectedat5dayspost-ischemia.IschemicpreconditioningmaintainedcalbindinD28kimmunoreactivityaftertransientcerebralischemia.Thesefindingssuggestthatischemicpreconditioningcanattenuatetransientcerebralischemia-causeddamagetothepyramidalneuronsinthehippocampalCA1areathroughmaintainingcalbindinD28kimmunoreactivity.